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Analysis of methods for growth detection in the search for extraterrestrial life.

In the search for life on other planets, experiments designed to detect the growth of microorganisms may prove to be definitive when coupled with chemical characterization and metabolic experiments. If organisms are not abundant, growth provides the only means for obtaining a large mass of biological material suitable for chemical compositional analyses and metabolic assays. Several methods of monitoring growth are described. Of these, optical monitoring in a unique system free of soil particles is advanced as the most appropriate. Theoretical problems related to the formulation of culture media are discussed, and several possible solutions are proposed. The sampling system, the type of monitoring, the size and placement of inoculum, and the medium volume and composition are contingent upon one another and must be integrated without sacrifice to the biological demands.

Culture Media↗

Optic nerve hypoplasia: associations and management.

Since its first description optic nerve hypoplasia has been identified with increasing frequency, and a range of associated problems have been described. The major neurological and endocrine associations are well established, but those factors that predispose to the development of optic nerve hypoplasia remain unclear. To understand the aetiology of these problems better, and to formulate a management regime, we studied a consecutive series of 40 patients who were divided into three groups. Group 1 (n = 24) had severe bilateral optic nerve hypoplasia; group 2 (n = 10) had mild, bilateral optic nerve hypoplasia; and group 3 (n = 6) had unilateral optic nerve hypoplasia. Previously described aetiological factors (for example, low maternal age or maternal alcohol or drug ingestion) were not present in any of the groups; this removes the need to screen a specific population. It is important that careful neurological and developmental assessments are carried out in children with optic nerve hypoplasia to identify potential disease. The role of imaging is discussed.

Child↗

Template learning of cellular neural network using genetic programming.

A new learning algorithm for space invariant Uncoupled Cellular Neural Network is introduced. Learning is formulated as an optimization problem. Genetic Programming has been selected for creating new knowledge because they allow the system to find new rules both near to good ones and far from them, looking for unknown good control actions. According to the lattice Cellular Neural Network architecture, Genetic Programming will be used in deriving the Cloning Template. Exploration of any stable domain is possible by the current approach. Details of the algorithm are discussed and several application results are shown.

Algorithms↗

What size should a bacterium be? A question of scale.

There are living prokaryotes (Bacteria and Archaea) that have cell sizes that range from 0.02-400 microns3. Over this tremendous range, various abilities to cope with the environment are needed. This review attempts to formulate some of the problems and some of the solutions. The smallest size for a free-living organism is suggested to be largely set by the catalytic efficiency of enzymes and protein synthetic machinery. Because of fluctuations in the environment, cells must maintain machinery to cope with various catastrophes; these mechanisms increase the minimum size of the cell. On the other hand, the largest cell is reasonably assumed to be limited by the ability of diffusion to bring nutrients to the appropriate part of the cell and to dispose of waste products. To explore the limitation imposed by diffusion, analysis is developed of diffusion processes through stirred and unstirred media, diffusion through media that contains obstacles, and the effect of size and shape.

Adaptation, Biological↗

Socioeconomic and political issues in radiology: a historical analysis.

Radiology literature indexes were searched for articles concerning socioeconomic and political issues published during two 21-year periods: 1920-1940 and 1970-1990. Of 200 articles found, 96 were considered appropriate for study, 40 from 1920-1940 and 56 from 1970-1990. All except two of the articles were from Radiology or the American Journal of Roentgenology. The articles were organized into 16 categories. By quantifying the number of times these socioeconomic and political issues appeared and comparing quotations from the articles, the authors demonstrated many common issues in the two periods, despite drastic differences in radiology practice. Analysis of historical literature provides perspective on current socioeconomic and political issues and may help formulate solutions to current problems. Documentation of such issues facilitates historical analysis and is an important function of the radiology literature.

Bibliometrics↗

A new method for continual quantitation of viable cells on endothelialized polyurethanes.

Many of the segmented polyurethanes currently used in cardiovascular prostheses undergo either modification of their surface structure or are lined with a confluent monolayer of endothelial cells to improve their hemocompatibility. During the establishment of an endothelial cell lining on these biopolymers it is necessary to continually monitor the number of viable cells that are covering the substrate. Yet, not all of the conventional cell enumeration techniques are suitable for assessing the growth of endothelial cells on polyurethanes. Methods, such as direct cell counting, dye uptake, or DNA or protein staining require either a transparent scaffold or lead to termination of the culturing process prior to measurement. In addition, some of the spectroscopic assays are often hampered by interaction of the dyes and/or solubilizers with the various constituents (e.g., catalyzers, antioxidants) and/or functional groups in the polyurethane formulations. In addressing these problems, we adapted a novel, highly reproducible fluorescent assay which is based on reduction by viable cells of an electrochemically sensitive compound, Alamar Blue. The bioreduced product is soluble and stable in culture media and noncytotoxic. In addition, the assay is independent of the geometry or physicochemical properties of the polymeric surfaces. In the present study we focus on the implementation of this assay to monitoring attachment and growth of various endothelial cell types on segmented polyurethanes.

Analysis of Variance↗

The concept of drug automatism.

The drug-automatism hypothesis implies a medication-induced absence of intentionality for self-poisoning and a relative amnesia for serial or single overdosage. Controversy stems from problems encountered in the formulation and verfication of the hypothesis. The author reviews the literature, presents a case associated with a proprietary sleeping preparation, and discusses psychopharmacological and psychophysiological elements in the mechanism of drug automatism and its differential diagnosis.

Amnesia, Retrograde↗

The ethics of therapeutic modality choice.

Psychiatrists usually select therapeutic modalities for their patients on the basis of empirical and theoretical considerations. Only in special circumstances (e.g., psychosurgery) are ethical concerns primary. Yet every therapeutic decision involves questions of value and requires ethical justification. The author outlines four resources for ethical direction in therapy: a general systems or biopsychosocial formulation of the clinical problem, the historic ethical commitments of the medical profession, the patient's informed perspective, and the psychiatrist's own values. Finally, a method is proposed for the resolution of conflicts among these four perspectives in individual cases.

Attitude of Health Personnel↗

Principles of mental health care for elderly inpatients.

Although the elderly's need for psychiatric treatment has long been recognized, publicly funded community mental health centers generally have been unsuccessful in establishing geriatric programs. If properly used, state mental hospitals remain a potential resource, but the more appropriate community-based placement of mentally impaired elderly persons is in special psychiatric units of general hospitals or in geropsychiatric units of private psychiatric hospitals. Principles for establishing such units in either setting include organizing a treatment team that empathizes with older patients and that has been trained to deal with the complex problems of the elderly. Formulation of comprehensive diagnoses and prognoses may require consultation and facilities outside the hospital; treatment planning should involve the patient's family from the beginning. Follow-up and supervision of referral after the patient's discharge are essential to the program's success.

Aged↗

A computer program for parenteral nutrition solution preparation.

The preparation of single-bottle parenteral nutrition solutions for neonates has long posed a problem for pharmacists. Frequent formulation changes and the need for rapid supply of solutions after prescription has led to a variety of preparation techniques being developed. An interactive computer program is described which enables a nonspecialist pharmacist staff to safely and quickly produce the formula, label and fully document it from a prescription for parenteral nutrition. Ordered quantities are expressed in amounts required per kilogram per 24 hours, and are input to a computer using a "prompt" system. Features of the program include automatic compensations for all non-amino acid ingredients of a variety of commercial amino acid solutions; specified or unspecified chloride anion input; and logic checks which are tied to physiologie "danger" levels, signaling to the operator when "greater than a critical level" has been requested by the prescriber, as well as the conventional check of the logic. The program has allowed infinite variability to prescribing of all ingredients of parenteral nutrition, extremely rapid and accurate production of formulate and allows the computer storage of data about nutritional input to patients. The program is extremely simple in operation, and gives significant cuts in lag time between prescription and the commencement of the new formula.

Carbohydrates↗

Artificial ants deposit pheromone to search for regulatory DNA elements.

BACKGROUND: Identification of transcription-factor binding motifs (DNA sequences) can be formulated as a combinatorial problem, where an efficient algorithm is indispensable to predict the role of multiple binding motifs. An ant algorithm is a biology-inspired computational technique, through which a combinatorial problem is solved by mimicking the behavior of social insects such as ants. We developed a unique version of ant algorithms to select a set of binding motifs by considering a potential contribution of each of all random DNA sequences of 4- to 7-bp in length. RESULTS: Human chondrogenesis was used as a model system. The results revealed that the ant algorithm was able to identify biologically known binding motifs in chondrogenesis such as AP-1, NFkappaB, and sox9. Some of the predicted motifs were identical to those previously derived with the genetic algorithm. Unlike the genetic algorithm, however, the ant algorithm was able to evaluate a contribution of individual binding motifs as a spectrum of distributed information and predict core consensus motifs from a wider DNA pool. CONCLUSION: The ant algorithm offers an efficient, reproducible procedure to predict a role of individual transcription-factor binding motifs using a unique definition of artificial ants.

5' Untranslated Regions↗

Ethical considerations in the design and execution of the National and Hispanic Health and Nutrition Examination Survey (HANES).

The purpose of this article is to describe some ethical considerations that have arisen during the design and implementation of the health examination surveys conducted by the National Center for Health Statistics of the Centers for Disease Control and Prevention. Three major areas of concern are discussed: sharing information from the study, banking and using banked tissue samples, and obligations for future testing of subjects. Specific concerns of sharing information include: when to inform, whom to inform, maintaining confidentiality, and how to inform individuals. Specific concerns of determining when sera will be banked and using banked samples include: depletion of samples for quality control, obtaining informed consent for unanticipated uses, access by others, and requests for batches of samples. Finally, specific concerns regarding future testing of subjects include: retesting for verification, retesting for interpretation, testing for different risk factors, and follow-up. Although existing surveys can provide experience or even suggest guidelines, the uniqueness of any new survey will generate unique ethical problems, requiring the careful formulation of unique solutions.

Ethics, Medical↗

Clinical trials of chemotherapy for falciparum malaria.

Plasmodium falciparum remains one of the World's most prevalent and devastating pathogens. Mainly for economic reasons, the parasite's ability to develop resistance to drugs has not been matched by the rate at which new compounds are developed. Even so, there are new drugs (or new combinations of old drugs) currently under investigation, or in the process of development (at the moment): Pyronaridine, a well-tolerated, synthetic drug that may have utility for multi-resistant falciparum malaria in many parts of the world; however,problems remain over the formulation of this drug (which is a major determinant of its bioavailability) and its eventual cost. Chlorproguanil-dapsone (lap dap) is being studied as a possible low-cost'successor' to pyrimethamine-sulfadoxine; the utility of chlorproguanil-dapsone as 'salvage' therapy for clinical cases of pyrimethamine-sulfadoxine failure has yet to be tested in clinical trials. Atovaquone-proguanil (malarone) has utility against multi-resistant parasites; however, it is likely to be expensive (but is currently being provided free-of-charge in certain areas of Africa). Artemether-benflumetol (coartemether) combines the advantages of artemether (a rapid reduction in parasite load) with a second drug that reduces the risk of recrudescence; the cost of this combination is unclear. Rectal artesunate is being studied as an intervention to reduce the proportion of children with falciparum malaria who deteriorate to severe disease; the formulation is appropriate for use in rural health centres.

Journal Article↗

[A practical study of the efficacy of a delayed-action preparation of carbamazepine (Tegretol CR 400) in the treatment of patients with partial epilepsy ].

INTRODUCTION: Carbamazepine (CBZ) is the first choice antiepileptic drug in the treatment of partial seizures. Many clinical studies show high efficacy and good tolerance of CBZ in the majority of patients. However, poor water solubility and erratic absorption as well as autoinduction of its metabolism, cause wide and unpredictable fluctuations in CBZ serum concentration. In order to avoid these problems controlled-release formulations of CBZ (Tegretol CR 400) were developed. PURPOSE: The aim of this study was to evaluate the efficacy, tolerance and practicality of the therapy of partial seizures in adults with controlled-release CBZ (Tegretol CR 400). PATIENTS AND METHODS: Over a three-year period we conducted an open pragmatic study of controlled-release CBZ in the therapy of 141 adult patients with established diagnosis of localized related epilepsy. Patients with progressive brain or systemic disease were excluded. All patients had unacceptable seizure frequency and were divided into four groups: 1) 34 with newly-diagnosed epilepsy; 2) 42 with chronic epilepsy and no previous antiepileptic medication; 3) 27 with chronic epilepsy previously treated with conventional preparations of carbamazepine (CBZ); and 4) 38 with chronic epilepsy previously treated with other antiepileptic medications. Patients were switched to controlled-release CBZ and the dosage was slowly adjusted. Baseline evaluation included the analysis of efficacy, tolerance and practicality of the controlled-release CBZ therapy. Three categories of efficiency were defined: 1) successful (patients without seizures); 2) partially successful (patients with improvement of at least 50% in frequency and severity of seizures); and 3) unsuccessful therapy (same or worse than before controlled-release CBZ). Tolerance and practicity were evaluated through the analysis of side effects and frequency of daily doses, respectively. These variables were compared to the corresponding ones after a period of at least three months of full dosage controlled-release CBZ therapy. RESULTS: In all four groups the therapy was successful in 76%, 52%, 30% and 29%, partially successful in 18%, 43%, 30% and 32%, and unsuccessful in 6%, S%, 40% and 39%, respectfully. Side effects occurred less frequently in all 4 groups during the therapy with controlled-release CBZ. We found reduced frequency of drug administration (once or twice daily) in 97.9% of our patients. DISCUSSION: Due to its slow and irregular absorption, short half life, wide and unpredictable fluctuation in plasma levels CBZ has decreased ability to control seizures, with the appearance of the intermittent side-effects such as diplopia, ataxia, headache and dizziness. Controlled-release formulation of CBZ sustains stable absorption and reduces fluctuations in carbamazepine serum concentration. Steady serum levels permit to the majority of patients to tolerate a higher total daily dose by reducing peak-dependent side-effects and improve compliance as a result of less frequent daily doses (1 or 2). CONCLUSION: In patients with partial seizures controlled-release vs. conventional carbamazepine had better efficiency, based on an excellent tolerance, favorable daily dosage and superior compliance.

Adolescent↗

Splendid spaces.

Welcome to FM's third gallery exhibit of visually impressive & beautifully functional noncommercial foodservice design projects. The five new & renovated facilities on display are among the most interesting recent designs formulated to solve operational problems such as congested flow, restricted space and poor lighting. Wander through the gallery & observe how careful planning & architectural ingenuity have been arranged to create striking compositions of splendid space.

Efficiency↗

Index selection with proportionality constraints.

Tallis [1962] formulated and solved the problem of constructing a selection index whose use will produce changes in the means of genotypic values of various traits that are proportional to ultimately desired changes. Several meaningful variations of this problem are described, and their solutions are presented in a common framework.

Animals↗

Single-dose pharmacokinetics of enteric-coated didanosine in HIV-infected children.

Didanosine remains a cornerstone nucleoside analogue for the treatment of HIV infection. A potential problem with the buffered formulations of didanosine is the likelihood of interactions with other drugs that require an acidic pH for absorption or can be chelated by cations in the buffer. An encapsulated enteric-coated (EC) bead formulation of didanosine has been approved and is routinely used as an alternative to the chewable/dispersible buffered tablet formulation. The objective of this study was to evaluate the single-dose pharmacokinetics of didanosine EC at 240 mg/m2 in 10 HIV-infected children. Didanosine EC was administered at time 0 on an empty stomach with no other concomitant medications. Blood samples were collected at pre-dose, 0.5, 1, 2, 4, 8 and 12 h post-dose. Didanosine was measured in plasma using radioimmunoassay. Ten subjects completed the intensive pharmacokinetic evaluation; data are available for eight participants. Plasma concentrations of didanosine following EC administration were analysed using non-compartmental methods. Median (range) AUCinfinity, Cmax, Tmax and CL/F for didanosine following EC administration were 2385 (1291, 3966) ng x h/ml, 854 (300, 1799) ng/ml, 3.0 (1.0, 8.1) h and 3.3 (2.7-6.4) l/h/kg, respectively. Results from this study indicate that the didanosine Cmax is decreased and Tmax is prolonged, but total exposure of didanosine in plasma following didanosine EC administration appears similar to previous data collected in HIV-infected children following buffered didanosine administration.

Anti-HIV Agents↗

Protein threading by linear programming.

Protein three-dimensional structure prediction through threading approach has been extensively studied and various models and algorithms have been proposed. In order to further explore ways to improve accuracy and efficiency of the threading process, this paper investigates the effectiveness of a new method: protein threading via linear programming. Based on the contact map model of protein 3D structure, we formulate the protein threading problem as a large scale integer programming problem, then relax to a linear programming problem, and finally solve the integer program by a branch-and-bound method. The final solution is optimal with respect to energy functions incorporating pairwise interaction and allowing variable gaps. The algorithm has been implemented as software package RAPTOR--RApid Protein Threading predictOR. Experimental results for fold recognition show that RAPTOR significantly outperforms other programs at the fold similarity level. The RAPTOR webserver is at http://www.cs.uwaterloo.ca/-j3xu/RAPTOR_form.htm.

Algorithms↗